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Methylmalonic acidemia (MMA) in pregnancy: a case series and literature review

  • Original Article
  • Published:
Journal of Inherited Metabolic Disease

Abstract

Introduction

Women with inherited metabolic disorders, including those with previously life-limiting conditions such as MMA, are reaching child-bearing age more often due to advances in early diagnosis and improved pediatric care. Information surrounding maternal and fetal complications associated with the underlying disorders remains largely unexplored.

Methods

Pregnancies affected by maternal MMA were ascertained through study 04-HG-0127 “Clinical and Basic Investigations of Methylmalonic Acidemia and Related Disorders” (clinicaltrials.gov identifier: NCT00078078) and via literature review. Prenatal and delivery records in study participants were reviewed.

Results

Seventeen pregnancies were identified in women with isolated MMA, including three abortions, one termination, and 13 completed pregnancies [three cases with cblA (four pregnancies), four cases of mut- (one cobalamin responsive, three non-responsive), five cases with unknown type of MMA]. Seventeen percent (3/17) of the pregnancies resulted in a first trimester abortion, while 38.5 % (5/13) of the completed pregnancies resulted in preterm deliveries. A cesarean delivery rate of 53.8 % (7/13) was noted among the cohort. Fetal distress or nonreassuring fetal status was the indication for 57 % (4/7) cesarean deliveries. One patient was reported to have metabolic crisis as well as episodes of mild hyperammonemia. Malformations or adverse outcomes in the progeny were not observed.

Conclusion

Although there have been a small number of pregnancies identified in women with MMA, the cumulative results suggest that the majority of pregnancies can be complicated by cesarean delivery and increased risk of prematurity. A pregnancy registry could clarify perinatal complications and define management approaches needed to ensure optimal maternal and fetal outcomes in this growing patient population.

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Compliance with ethics guideline

Conflict of interest

None.

Human and animal rights and informed consent

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (National Institutes of Health, National Human Genome Research Institute) and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from all patients included in the study.

Author information

Authors and Affiliations

  1. Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA

    Donna B. Raval, Jennifer L. Sloan, Irini Manoli & Charles P. Venditti

  2. Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Medstar Washington Hospital Center, Washington, DC, USA

    Donna B. Raval

  3. Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA

    Melissa Merideth

  4. Department of Human Genetics and Pediatrics, McGill University-Montreal Children’s Hospital Research Institute, Montreal, QC, Canada

    Nancy E. Braverman

  5. Division of Genetic, Genomic, andMetabolic Disorders, Children’s Hospital of Michigan, Department of Pediatrics, Wayne State University School of Medicine, Detroit, MI, USA

    Robert L. Conway

Authors
  1. Donna B. Raval
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  2. Melissa Merideth
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  3. Jennifer L. Sloan
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  4. Nancy E. Braverman
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  5. Robert L. Conway
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  6. Irini Manoli
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  7. Charles P. Venditti
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Corresponding author

Correspondence to Charles P. Venditti.

Additional information

Communicated by: Brian Fowler

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Raval, D.B., Merideth, M., Sloan, J.L. et al. Methylmalonic acidemia (MMA) in pregnancy: a case series and literature review. J Inherit Metab Dis 38, 839–846 (2015). https://doi.org/10.1007/s10545-014-9802-8

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  • DOI: https://doi.org/10.1007/s10545-014-9802-8

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